title: The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing's disease from normal physiology.
abstract: The dexamethasone-suppressed CRH test (Dex-CRH test) differentiates patients with Cushing's syndrome (CS) from those with pseudo-Cushing states, who have decreased ACTH responses to CRH because of negative feedback exerted by chronic hypercortisolism. Normal subjects, however, have not been studied with the Dex-CRH test, raising concern that this test might not separate patients with CS from patients with normal adrenal function. To determine whether the criterion that separates CS from pseudo-Cushing states also would differentiate patients with Cushing's disease (CD) from individuals with eucortisolism, we studied 20 healthy volunteers during low-dose (2 mg/day) dexamethasone suppression, and then during the Dex-CRH test (CRH stimulation test performed 2 h after completion of low-dose dexamethasone suppression), and contrasted their results with those of 20 patients with surgically proven mild CD [urine free cortisol (UFC) < 1000 nmol/day). Basal UFC was significantly greater in patients with CD (P < 0.001) but within the normal range (55-250 nmol/day) in 4 patients. During low-dose dexamethasone suppression, a UFC less than 100 nmol/day (36 micrograms/day) was found in all but 1 volunteer subject, and a urine 17-hydroxycorticosteroid excretion less than 14.6 mumol/day (5.3 mg/day) was found in all but 2 subjects. During the Dex-CRH test, plasma cortisol less than 38 nmol/L was found in all 20 normal volunteers until 30 min after CRH administration. By contrast, the 15-min CRH-stimulated plasma cortisol exceeded 38 nmol/L in all patients with CD (P < 0.001). Plasma dexamethasone measured just before CRH administration was similar in normal volunteers (13.0 +/- 6.1 mumol/L) and patients with CD (16.4 +/- 6.4 mumol/L). We conclude that cortisol measurements obtained during the Dex-CRH test are suppressed in normal volunteers below those found in mild CD. These results suggest that the Dex-CRH test may be useful in the evaluation of CS in patients without significant hypercortisoluria. However, its value in patients with episodic hormonogenesis has not been tested.
authors.affiliation: Office of the Director, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA. yanovskj@cc1.nichd.nih.gov
authors.forename: J A
authors.initials: JA
authors.lastname: Yanovski
authors.forename: G B
authors.initials: GB
authors.lastname: Cutler
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
mesh_terms: D015065:17-Hydroxycorticosteroids / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone; D003480:Cushing Syndrome / Q000175:diagnosis*; D003907:Dexamethasone / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007700:Kinetics; D008297:Male; D008875:Middle Aged
chemical_list: D015065:17-Hydroxycorticosteroids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone